The ?3-D Retina Organoid'' Challenge (the ?Challenge''), is an ideation Challenge in which the National Eye Institute is asking for ideas to maximize the physiological relevance of 3-D human retina culture systems. Currently, retina culture models do not capture the complexity of the human retina. The goal of the Challenge is to transform innovative ideas into concrete concepts to develop new in vitro 3-D human retina models that recapitulate the organization and function of the human retina. NEI intends to follow this challenge with a follow-on but distinct Reduction to Practice Challenge, which will aim to invoke scientific and technological development of the model system. Technological breakthroughs in this arena could allow researchers and physicians to better understand, diagnose, and treat retinal diseases. Around the world, an estimated 285 million people are visually impaired; of these, 39 million are blind. In many cases, blindness and vision loss are the result of retina-damaging diseases that, if better understood, could be treated or have interventions applied to stop degeneration or provide protection to remaining viable cells. One limitation in furthering research in this area is that eye tissue to study disease processes is not readily available. However, retina biology researchers have developed methods to grow 3-D retina models in vitro from induced pluripotent stem cells (iPSC) and embryonic stem cells (ESC). Current protocols vary in their strengths and limitations, but none can robustly recapitulate the complexity and functionality of the retina. In this Challenge, NEI seeks concept solutions outlining methods and protocols to develop a 3-D human retina organoid prototype that is physiologically relevant. Protocols to develop such a model system could be transformational for vision research and regenerative medicine. New models could be used for applications such as understanding eye development, studying retinal biology, modeling diseases, identifying and testing treatments, and serving as a tissue source to use in transplantation. In this Challenge, the protocols to make models used for disease modeling and drug testing are desired, and solution(s) should yield protocols that allow reproducible culture of functionally-competent retina organoids. This Challenge will speed up the efforts toward this goal.